A significant population of patients with infertility has elevated gonadotropin levels associated with their hypogonadism, and has previously been though to have primary gonadal failure with irreversible infertility. However, pregnancies have intermittently been reported in this group of patients, with unknown pathophysiology. New techniques of pelvic ultrasonography, receptor and bioassays, and molecular biology now allow the identification of a spectrum of defects of gonadotropin action, rather than gonadal failure, in these patients. Pelvic ultrasonography has identified residual ovarian follicles in over half the women with hypergonadotropic hypogonadism in our series. A mutation of the LH beta- subunit gene has been identified in a man with abnormal receptor binding. In other patients, both LH and FSH receptor binding inhibitors have been identified. Once such defects are documented, these patients have the potential for gonadal responsiveness if the gonadal stimulus can be corrected. This project seeks to use pelvic ultrasonography and gonadotropin receptor assays to screen hypergonadotropic patients for evidence of ovarian folliculogenesis or abnormal gonadotropin receptor binding to establish the frequency of such abnormalities. Patients with abnormal receptor binding will then be studied further to purify the gonadotropin modulators or binding inhibitors and to identify the specific gene defects, so that specific treatments can ultimately be developed. Both men and women with hypergonadotropic hypogonadism will be enrolled for a period of observation, to characterize the known waxing and waning course of gonadal failure, followed by subsequent treatment with appropriate sex steroid replacement, to suppress their endogenous gonadotropins. during the trial, serial examinations and receptor assays will be performed in an effort to more carefully characterize the pathophysiology and to identify clinical and biochemical parameters that will be predictive of therapeutic responsiveness.